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Rapid Reduction of ₁-Receptor Binding and ¹⁸F-FDG Uptake in Rat Gliomas After In Vivo Treatment with Doxorubicin

¹ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ² Division of Tracer Kinetics, Advanced Science Research Center, Central Institute of Radioisotopes Science, Kanazawa University, Kanazawa, Japan; and ³ Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Correspondence: For correspondence contact: Aren van Waarde, PhD, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands. E-mail: a.van.waarde{at}pet.umcg.nl

-Receptors are strongly overexpressed in most rodent and human tumors and are proliferation markers. To evaluate the potential of a radiolabeled ₁-ligand for therapy monitoring, we compared early changes of ¹¹C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (¹¹C-SA4503) binding and ¹⁸F-FDG uptake in gliomas after in vivo chemotherapy. Methods: C6 cells (2.5 x 10⁶) were subcutaneously injected into the right shoulder of male Wistar rats. After 7 d, the tumor volume was 0.60 ± 0.08 cm³. Animals then received either saline or doxorubicin (8 mg/kg, intraperitoneally). One control and 1 treated rat were imaged simultaneously, 24 or 48 h after treatment, under pentobarbital anesthesia. Rodents (n = 20) were scanned first with ¹¹C-SA4503 (25 MBq, intravenously) followed more than 100 min afterward by ¹⁸F-FDG (20 MBq, intravenously), using a dedicated small-animal PET camera (60-min protocol, tumors in the field of view). Tumor homogenates were prepared and subjected to -receptor assays. The biodistribution of ¹⁸F-FDG was assessed. Results: Tumors appeared 4–5 d after inoculation and grew exponentially. No significant reduction of tumor growth was visible within 48 h after doxorubicin treatment. Both PET tracers visualized the tumors and showed reduced uptake after chemotherapy (¹¹C-SA4503: 26.5% ± 6.5% at 24 h, 26.5% ± 7.5% at 48 h; ¹⁸F-FDG: 22.6% ± 3.2% at 24 h, 27.4% ± 3.2% at 48 h; ex vivo ¹⁸F-FDG: 22.4% ± 5.4% at 24 h, 31.7% ± 12.7% at 48 h). ₁-Receptor density in treated tumors was also reduced (from 172 ± 35 to 125 ± 28 fmol/mg of protein). Conclusion: Both ¹¹C-SA4503 binding and ¹⁸F-FDG uptake declined in gliomas after chemotherapy. Decreased binding of ¹¹C-SA4503 corresponded to a loss of ₁-receptors from the tumors. Changes in tracer uptake preceded the morphologic changes by at least 48 h.

Key Words: ¹¹C-SA4503 • chemotherapy • tumor • doxorubicin • microPET

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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